Amyloid precursor protein products concentrate in a subset of exosomes specifically endocytosed by neurons
| Autor: | Gaëlle Lachenal, Rémy Sadoul, Béatrice Blot, Christine Chatellard, Fiona J. Hemming, Mathilde Chivet, Charlotte Javalet, Karine Laulagnier |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Amyloid beta Plaque Amyloid Exosomes Amyloid beta-Protein Precursor 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Tetraspanin Pregnancy mental disorders Amyloid precursor protein medicine Animals Humans Secretion Senile plaques Molecular Biology Cells Cultured Neurons Pharmacology Amyloid beta-Peptides biology Intercellular transport Brain Cell Biology Embryo Mammalian Molecular biology Endocytosis Microvesicles Rats Cell biology Protein Transport 030104 developmental biology medicine.anatomical_structure biology.protein Molecular Medicine Neuroglia Female 030217 neurology & neurosurgery |
| Zdroj: | Cellular and Molecular Life Sciences. 75:757-773 |
| ISSN: | 1420-9071 1420-682X |
| DOI: | 10.1007/s00018-017-2664-0 |
| Popis: | Amyloid beta peptide (Aβ), the main component of senile plaques of Alzheimer's disease brains, is produced by sequential cleavage of amyloid precursor protein (APP) and of its C-terminal fragments (CTFs). An unanswered question is how amyloidogenic peptides spread throughout the brain during the course of the disease. Here, we show that small lipid vesicles called exosomes, secreted in the extracellular milieu by cortical neurons, carry endogenous APP and are strikingly enriched in CTF-α and the newly characterized CTF-η. Exosomes from N2a cells expressing human APP with the autosomal dominant Swedish mutation contain Aβ peptides as well as CTF-α and CTF-η, while those from cells expressing the non-mutated form of APP only contain CTF-α and CTF-η. APP and CTFs are sorted into a subset of exosomes which lack the tetraspanin CD63 and specifically bind to dendrites of neurons, unlike exosomes carrying CD63 which bind to both neurons and glial cells. Thus, neuroblastoma cells secrete distinct populations of exosomes carrying different cargoes and targeting specific cell types. APP-carrying exosomes can be endocytosed by receiving cells, allowing the processing of APP acquired by exosomes to give rise to the APP intracellular domain (AICD). Thus, our results show for the first time that neuronal exosomes may indeed act as vehicles for the intercellular transport of APP and its catabolites. |
| Databáze: | OpenAIRE |
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